The aging of skin may be understood as being influenced by intrinsic factors and extrinsic factors. Intrinsic factors include natural changes to the skin, which are regulated by genetic makeup. Extrinsic factors include exogenous influences such as UV damage, environmental factors, and the like.
Aging of the skin can adversely affect elasticity and strength of the skin through changes in the two main constituents of the dermal extracellular matrix, the fibrous proteins collagen and elastin. For example, elastin is a large fibrous protein formed by the crosslinking of elastin precursor protein molecules (e.g., tropoelastin) into spiral filaments. The spiral filaments consist of peptidic chains that are capable of extending and then resuming their original shape.
Elastin is secreted by the fibroblasts of the dermal connective tissues into the extracellular matrix. However, the biosynthesis of elastin typically ceases at some point during adulthood. Furthermore, during intrinsic and extrinsic aging processes, elastin undergoes structural and compositional changes, e.g., the elastic fibers progressively degenerate and separate into fragments. The changes could manifest themselves by signs of aging, such as lines, wrinkles, loss of elasticity, sagging, skin dryness and unevenness, blotches, and age spots.
Certain agents are known for their beneficial effect of inhibiting the degradation of crosslinked elastin. For example, it is known that matrix metalloproteinases (MMPs), a group of enzymes that are able to break down macromolecules in the extracellular matrix, play an important role in elastin degradation. It has been found that the content of MMPs is markedly higher in old skin than in young skin. MMPs also play a critical role in the premature skin aging caused by exogenous factors. An even higher level of MMPs was detected in light-aged skin as compared with aged skin protected from the light. J. H. Chung et al., J. Invest. Dermatol. (2001) 117, 1218-1224. Studies have also shown that the levels of a series of matrix metalloproteinases (MMP-1, -3, -9 and -13) are significantly higher in patients with inflammation. T. Kuboto et al., Arch. Oral. Biol. (1996) 41, 253-262; A. L. Ejeil et al., J. Periodontol. (2003) 74, 188-195. Further, MMP-2 and MMP-9 were found to be the elastin-degrading proteases. Cosmetics & Toiletries (2000) 115 (11), 75-82).
A number of plant extracts have been described as inhibitors of various MMPs. For instance, J. L. Lamaison describes the inhibition of elastase (porcine pancreatic elastase) with extracts of plants selected from the rosaceae group and attributes the inhibition to the tannins they contain. Ann. Pharmaceutiques Francaises (1990) 48, 335-340.
M. Herrmann et al. discloses that SymMatrix, a hydroalcoholic blackberry leaf extract, exhibits the MMP-1, MMP-2, and MMP-9 inhibitory activity. SOFW Journal (2006) 132(4), 42-46.
In addition, certain natural or synthetic compounds are known for the beneficial effect of promoting the production of elastin precursor. For example, retinoids up-regulate elastin production in fibroblasts. Liu B, Harvey C S, McGowan S E. Am. J. Physiol. (1993 November) 265(5 Pt 1):L430-437.
Furthermore, it has also been noted that certain agents positively influence the cross-linking of tropoelastin. For example, lysyl oxidase serves as a crosslinking enzyme and an element of the scaffold to ensure spatially defined deposition of elastin. Liu, Xiaoqing et al., Nature Genetics (2004), 36(2), 178-182. Cenizo et al. discloses a dill extract that induces the lysyl oxidase (LOXL) gene expression, which is responsible for elastin cross-linking in adults. Experimental Dermatology (2006), 15(8), 574-81. Additionally, currant, cardamon, black radish, box holly, Asea foetida gum, ethyl hexenoate, methyl butyrate, and ethyl decadienoate are disclosed as promoters of LOXL gene expression. GB 2,438,999.
Thus, numerous pathways and agents have been proposed to positively influence elastin and skin-properties related thereto. However, the inventors have recognized that a surprisingly beneficial synergistic efficacy is obtained by topically applying a composition that includes both a tropoelastin promoter and a tropoelastin crosslinker.